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Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study (TRIDENT COG)

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ClinicalTrials.gov Identifier: NCT03785067
Recruitment Status : Not yet recruiting
First Posted : December 24, 2018
Last Update Posted : September 4, 2019
Sponsor:
Collaborator:
University of Sydney
Information provided by (Responsible Party):
The George Institute

Brief Summary:
A Sub-Study of an investigator initiated and conducted, multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial (TRIDENT) to determine the effect of more intensive long-term blood pressure control, provided by a fixed low-dose combination blood pressure lowering pill ("Triple Pill") strategy on top of standard of care, for slowing memory decline as measured by Cambridge Neuropsychological Test Automated Battery (CANTAB), in patients with a history of acute stroke due to intracerebral haemorrhage (ICH).

Condition or disease Intervention/treatment Phase
Cognitive Decline Intracerebral Hemorrhage Dementia, Vascular Cerebral Small Vessel Diseases Hypertension Stroke Hemorrhagic Drug: telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg Drug: Placebo oral capsule Phase 3

Detailed Description:

Cognitive decline and dementia in ICH is high due to the common underlying vasculopathy of cerebral small vessel disease (CSVD). However, in general, detailed cognitive outcomes in ICH have been neglected, possibly due to the high mortality rate of ICH (up to 60% within the first year).

Blood pressure (BP) management in those with ICH has been suboptimal. Most hypertensive patients need more than two medications. Combination therapy may improve adherence and BP reduction and reduce cardiovascular (CV) event rates. In the main TRIDENT study, it is hypothesised that a fixed low-dose triple combination BP-lowering agent, termed the 'Triple Pill' will prevent recurrent stroke. The Triple Pill is composed of a single capsule containing either a combination of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg, or placebo.

In addition to achieving optimal BP control, the Triple Pill also has the capacity to slow cognitive decline and dementia in ICH survivors. Research shows that elevated BP is associated with Alzheimer's disease and vascular dementia, even after accounting for prior stroke or transient ischaemic attack, and large scale prospective studies have shown a 50% reduction in dementia when BP is managed appropriately


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 403 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial.

Sub-Study: Multicentre, international, single-arm trial

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Main Study: Participants are double-blinded. Sub-Study: No blinding to neuropsychological assessments
Primary Purpose: Screening
Official Title: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study
Estimated Study Start Date : October 28, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Triple Pill (Active Treatment)

Main Study: Fixed low-dose combination BP-lowering pill ("Triple Pill") telmisartan 20mg + amlodipine 2.5mg + indapamide 1.25mg

Sub-Study: single-arm

Drug: telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg
1 capsule taken orally once daily for 36 months
Other Name: Triple Pill

Placebo Comparator: Placebo

Main Study: Matched placebo, received via blinded study capsules

Sub-Study: single-arm

Drug: Placebo oral capsule
1 capsule taken orally once daily for 36 months




Primary Outcome Measures :
  1. Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest [ Time Frame: Baseline, 18 and 36 months ]
    Raw scores and z-scores will be used. Change scores on the CANTAB PAL will be computed between baseline, 18 and 36 months (primary endpoint).


Secondary Outcome Measures :
  1. Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP) [ Time Frame: Baseline, 18 and 36 months ]
    Change scores will be computed for CANTAB RVP between baseline, 18 and 36 months

  2. Change scores will be computed for CANTAB Multi-tasking Test (MTT) [ Time Frame: Baseline, 18 and 36 months ]
    Change scores will be computed for CANTAB MTT between baseline, 18 and 36 months

  3. Change scores will be computed for gold-standard neuropsychological assessments [ Time Frame: Baseline, 18 and 36 months ]
    Change scores will be computed for gold-standard neuropsychological assessment between baseline, 18 and 36 months

  4. Diagnosis of all-cause dementia [ Time Frame: 36 months ]
    Diagnosis of all-cause dementia as determined by consensus of three blinded adjudicators based on established criteria following collection of data of the 3-year study period



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Eligible for, randomised and continuing in the TRIDENT Main Study
  2. Must be able to attend the site conducting the cognitive assessments. In Sydney, this will either be at the same site as where TRIDENT study is conducted or at the BMC, University of Sydney, Camperdown.
  3. Ability and willingness to undergo neuropsychological testing (i.e. have no major visual, auditory or motor impairments)
  4. Language spoken compatible with CANTAB administration (i.e. CANTAB will be administered in the local language(s) of the country in question. E.g. in Australia, the CANTAB will only be administered in English).
  5. Provision of written informed consent

Exclusion Criteria:

  1. Study medication has been permanently stopped prior to or at the 6-month visit of the TRIDENT main study
  2. Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313 or higher
  3. Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 2414.
  4. Evidence of rapid deterioration suggestive of dementia by decline of 3 points in MoCA assessments between randomisation and the 6-month study visit in the TRIDENT main study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03785067


Contacts
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Contact: Ruth Freed +61 2 8052 4522 rfreed@georgeinstitute.org.au
Contact: Grace Balicki +61280524811 gbalicki@georgeinstitute.org.au

Sponsors and Collaborators
The George Institute
University of Sydney
Investigators
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Principal Investigator: Prof Craig Anderson The George Institute
Principal Investigator: Prof Sharon Naismith University of Sydney

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Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT03785067     History of Changes
Other Study ID Numbers: TRIDENT COG
First Posted: December 24, 2018    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The George Institute:
TRIDENT
Additional relevant MeSH terms:
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Cerebral Hemorrhage
Cerebral Small Vessel Diseases
Dementia, Vascular
Hemorrhage
Cognitive Dysfunction
Vascular Diseases
Cardiovascular Diseases
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Pathologic Processes
Cognition Disorders
Intracranial Hemorrhages
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Amlodipine
Telmisartan
Indapamide
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents